There is an urgent need to identify and examine novel risk factors that can be utilized in the prevention and treatment of cardiovascular disease (CVD). Dr. Qi Sun has developed a strong interest in identifying novel biomedical and genetic risk factors for CVD and dedicated himself to a career in genetic and molecular epidemiology of CVD. To gain knowledge and skills necessary for the transition into an independent researcher in this field, Dr. Sun will implement a comprehensive training plan encompassing advanced course work in genetic epidemiology, attendance at seminars and research conferences, close interactions with mentors, and other significant research activities in the mentored K99 phase of this career development award. Drs. Frank Hu and James Meigs, two well-established researchers and highly experienced trainers, will serve as the mentors. The Harvard School of Public Health will provide an ideal environment for Dr. Sun's training and career development. The Harvard medical community houses a rich collection of established investigators with expertise in various areas who will provide additional training to Dr. Sun. The training activities will focus on acquiring knowledge and skills in genetic epidemiology, as well as expertise on epidemiologic study design and statistical analysis of genetic data. This training is necessary and essential for Dr. Sun's development into an independent scientist capable of using interdisciplinary approaches to addressing research questions in molecular and genetic CVD epidemiology. During the R00 phase of this award, Dr. Sun proposes to assay and examine three novel adipokines, i.e., retinol binding protein 4, fatty acid binding protein 4, and high-molecular-weight adiponectin, in plasma in relation to coronary heart disease (CHD) among type 2 diabetic patients in two large prospective cohorts. In addition, Dr. Sun will conduct whole-genome association (GWA) studies to search for genetic determinants for these biomarkers and subsequently utilize identified genetic variants to corroborate biomarker-disease associations and to examine gene-environment interactions. These biomarkers are identified in animal studies and proven to play causal roles in the etiology of CHD. However, lack of prospective human data limits the use of these molecules in the treatment and prevention of CHD in humans. The genetic studies will greatly deepen the understanding of genetic regulation on these molecules and facilitate the identification of high-risk populations. The proposed studies will provide timely and critical data that can be directly translated into CHD prevention and treatment strategies and, thus, are highly relevant to the mission of NHLBI. PUBLIC HEALTH RELEVANCE: Coronary heart disease is an even stronger cause of death in diabetic patients than in the general population. As traditional CHD risk factors fail to explain all of the excess CHD risk among diabetic patients, identification of novel risk factors has become critical for disease treatment and prevention. Novel adipokines are promising candidates that are worth investigating in prospective human studies.